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Wednesday, May 10, 2017

Mechanistic Modeling Quantifies The Influence Of Tumor Growth Kinetics On The Response To Anti-Angiogenic Treatment

Mechanistic Modeling Quantifies The Influence Of Tumor Growth Kinetics On The Response To Anti-Angiogenic Treatment

Thomas D.Gaddy, Stacey D.Finley

Abstract

Tumors
exploit angiogenesis, the formation of new blood vessels from
pre-existing vasculature, in order to obtain nutrients required for
continued growth and proliferation. Targeting factors that regulate
angiogenesis, including the potent promoter vascular endothelial growth
factor (VEGF), is therefore an attractive strategy for inhibiting tumor
growth. Systems biology modeling enables us to identify tumor-specific
properties that influence the response to those anti-angiogenic
strategies. Here, we build on our previous systems biology model of VEGF
transport and kinetics in tumor-bearing mice to include a tumor
compartment whose volume depends on the “angiogenic signal” produced
when VEGF binds to its receptors on tumor endothelial cells. We trained
and validated the model using in vivo measurements of xenograft tumor
volume to produce a model that accurately predicts the tumor's response
to anti-angiogenic treatment. We applied the model to investigate how
tumor growth kinetics influence the response to anti-angiogenic
treatment targeting VEGF. Based on multivariate regression analysis, we
found that certain intrinsic kinetic parameters that characterize the
growth of tumors could successfully predict response to anti-VEGF
treatment. This model is a useful tool for predicting which tumors will
respond to anti-VEGF treatment, complementing pre-clinical in vivo
studies.